Quantitative Comparative Proteomics Reveal Biomarkers for Dengue Disease Severity.

Dengue fever (DF) could develop into dengue haemorrhagic fever (DHF) with increased mortality rate. Since the clinical characteristics and pathogen are same in DF and DHF. It's important to identify different molecular biomarkers to predict DHF patients from DF. We conducted a clinical plasma proteomics study using quantification (TMT)-based quantitative proteomics methodology to found the differential expressed protein in DF patients before they developed into DHF. In total 441 proteins were identified up or down regulated. There proteins are enriched in diverse biological processes such as proteasome pathway, Alanine, aspartate, and glutamate metabolism and arginine biosynthesis. Several proteins such as PLAT, LAMB2, and F9 were upregulated in only DF patients which developed into DHF cases, not in DF, compared with healthy-control. In another way, FGL1, MFAP4, GLUL, and VCAM1 were upregulated in both DHF and DF cases compare with healthy-control. RT-PCR and ELISA were used to validate these upregulated gene expression and protein level in 54 individuals. Results displayed the same pattern as proteomics analysis. All including PLAT, LAMB2, F9, VCAM1, FGL1, MFAP4, and GLUL could be considered as potential markers of predicting DHF since the levels of these proteins vary between DF and DHF. These new founding identified potential molecular biomarkers for future development in precision prediction of DHF in DF patients.